The effects of interleukin-6 (IL-6) on the liver synthesis of thyroid- hormone binding proteins was investigated by biosynthetic labeling of human hepatoblastoma-derived Hep G2 cells using [35-S] methionine, followed by immunoprecipitation of media with specific antisera, and fluorography of immunoprecipitates. Slot blot hybridization of mRNAs to specific cDNAs was also carried out. IL-6 produced a dose and time-dependent inhibition of T4 binding globulin, albumin and transthyretin. Similar effects were exerted on corticosteroid- binding globulin. On the other hand, IL-6 increased alpha 1-antitrypsin and alpha 1-antichymotrypsin synthesis. These effects appeared to occur mainly at a pretranslational level. The activity of IL-6 could be inhibited by preincubation with neutralizing anti-IL6 antiserum, and could be reverted by removing the cytokine from the culture medium.